The present invention relates to a medical treatment of diabetic vascular complications, and particularly to a method for treating diabetic vascular complications with an extract product of a Dioscorea species.
Non-enzymatic glycation (Maillard reaction) has been implicated in the pathogenesis of diabetic vascular complications. Recent immunohistochemical studies have shown that the formation of advanced glycation end product (AGE) is enhanced in diabetic subjects (Liu et al., Diabetes. 48: 2074-2082, 1999). AGE formation per se is known to alter the structural and functional properties of the tissue protein. In addition, the interaction between AGE-modified proteins and various types of cells is thought to play a pathological role in the abnormalities observed in diabetic subjects. Therefore, an excessive accumulation of AGE in the body has been suggested as a main factor for triggering diabetic vascular complications such as atherosclerotic lesions, nephropathy, vessel injury, neuropathy and retinopathy (Vlassara et al., Journal of Internal Medicine 251: 87-101, 2002).
Chronic hyperglycemia is essentially involved in the development and progression of diabetic vascular complications. In the liver, endocytosis of AGE-modified protein leads to loss of scavenger receptors and delayed intracellular transport in hepatic sinusoidal endothelial cells. (Hansen et al., Diabetologia 45:1379-1388, 2002) In the kidney, AGE-modified type IV collagen and laminin reduce their ability to interact with negatively charged proteoglycans, increasing vascular permeability to albumin. (Silbiger et al., Kidney Int 43: 853-64, 1993)
To date, there have been several approaches which seek to prevent AGE formation, reduce AGE effects on cells and break pre-existing AGE crosslinks. An important pharmacological strategy has utilized the small nucleophilic hydrazine compound aminoguanidine, a potent inhibitor of AGE-mediated crosslinking. Another AGE-inhibiting drug is still under development including the thiazolidine derivative OPB-9195 which has been shown to prevent the progression of diabetic glomerulosclerosis in rats. An angiotensin converting enzyme inhibitor (ACEI), such as rampril has also been found to alleviate the nephropathy in diabetic mice treated with streptozotocin (STZ).
Although the compounds or drugs developed so far have been directed to inhibit formation of AGE and AGE cross-linking, the existing AGE is not cleared by the specific compounds or the drugs remain to damage the cells and tissues in the diabetic subject. It is also difficult to establish the toxicity and side effects associated with the compounds or drugs administered in the diabetic subject.
Dioscorea is one of the very important pharmaceutical plants used in traditional Chinese medicine, and the medicinal effects thereof have been studied for years. In 1936, Tsukamoto et al isolated diosgenin, a steroid saponin of Dioscorea, from the Dioscoreacea family of plants and used the isolated diosgenin as a raw material for rapid synthesis of medicinal steroids. However, no study has yet been conducted using an extract product of Dioscorea in the treatment of diabetic vascular complications.